Evolutionary trajectory of TRPM2 channel activation by adenosine diphosphate ribose and calcium.

Ion channel activation upon ligand gating triggers a myriad of biological events and, therefore, evolution of ligand gating mechanism is of fundamental importance. TRPM2, a typical ancient ion channel, is activated by adenosine diphosphate ribose (ADPR) and calcium and its activation has evolved from a simple mode in invertebrates to a more complex one in vertebrates, but the evolutionary process is still unknown. Molecular evolutionary analysis of TRPM2s from more than 280 different animal species has revealed that, the C-terminal NUDT9-H domain has evolved from an enzyme to a ligand binding site for activation, while the N-terminal MHR domain maintains a conserved ligand binding site. Calcium gating pattern has also evolved, from one Ca2+-binding site as in sea anemones to three sites as in human. Importantly, we identified a new group represented by olTRPM2, which has a novel gating mode and fills the missing link of the channel gating evolution. We conclude that the TRPM2 ligand binding or activation mode evolved through at least three identifiable stages in the past billion years from simple to complicated and coordinated. Such findings benefit the evolutionary investigations of other channels and proteins.

Early detection and prognosis evaluation for hepatocellular carcinoma by circulating tumour DNA methylation: A multicentre cohort study.

BACKGROUND: Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC. METHODS: A three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP). RESULTS: Genome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre- and postoperative plasma samples from 103 HCC patients and correlated with 2-year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p < .001). CONCLUSIONS: HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC-specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at-risk populations.

Establishing subdivisions of M1 stage nasopharyngeal carcinoma based on decision tree classification: A multicenter retrospective study.

OBJECTIVES: To meet the demand for personalized treatment, effective stratification of patients with metastatic nasopharyngeal carcinoma (mNPC) is essential. Hence, our study aimed to establish an M1 subdivision for prognostic prediction and treatment planning in patients with mNPC. MATERIALS AND METHODS: This study included 1239 patients with mNPC from three medical centers divided into the synchronous mNPC cohort (smNPC, n = 556) to establish an M1 stage subdivision and the metachronous mNPC cohort (mmNPC, n = 683) to validate this subdivision. The primary endpoint was overall survival. Univariate and multivariate Cox analyses identified covariates for the decision-tree model, proposing an M1 subdivision. Model performance was evaluated using time-dependent receiver operating characteristic curves, Harrell's concordance index, calibration plots, and decision curve analyses. RESULTS: The proposed M1 subdivisions were M1a (≤5 metastatic lesions), M1b (>5 metastatic lesions + absent liver metastases), and M1c (>5 metastatic lesions + existing liver metastases) with median OS of 34, 22, and 13 months, respectively (p < 0.001). This M1 subdivision demonstrated superior discrimination (C-index = 0.698; 3-year AUC = 0.707) and clinical utility over those of existing staging systems. Calibration curves exhibited satisfactory agreement between predictions and actual observations. Internal and mmNPC cohort validation confirmed the robustness. Survival benefits from local metastatic treatment were observed in M1a, while immunotherapy improved survival in patients with M1b and M1c disease. CONCLUSION: This novel M1 staging strategy provides a refined approach for prognostic prediction and treatment planning in patients with mNPC, emphasizing the potential benefits of local and immunotherapeutic interventions based on individualized risk stratification.

Design, synthesis, and biological evaluation of novel benzimidazole derivatives as anti-cervical cancer agents through PI3K/Akt/mTOR pathway and tubulin inhibition.

Phosphatidylinositol 3-kinase (PI3K) is one of the most attractive therapeutic targets for cervical cancer treatment. In this study, we designed and synthesized a series of benzimidazole derivatives and evaluated their anti-cervical cancer activity. Compound 4r exhibited strong antiproliferative activity in different cervical cancer cell lines HeLa, SiHa and Ca Ski, and relative lower cytotoxicity to normal hepatic and renal cell lines LO2 and HEK-293t (IC50 values were at 21.08 µM and 23.96 µM respectively). Its IC50 value was at 3.38 µM to the SiHa cells. Further mechanistic studies revealed that 4r induced apoptosis, arrested cell cycle in G2/M phase, suppressed PI3K/Akt/mTOR pathway and inhibit the polymerization of tubulin. Molecular docking study suggested that 4r formed key H-bonds action with PI3Kα (PDB ID:8EXU) and tubulin (PDB ID:1SA0). Zebrafish acute toxicity experiments showed that high concentrations of 4r did not cause death or malformation of zebrafish embryos. All these results demonstrated that 4r would be a promising lead candidate for further development of novel PI3K and tubulin dual inhibitors in cervical cancer treatment.

Knowledge, Attitudes and Practices Toward Physical Literacy Among the College Students During COVID-19 School Closure.

Purpose: To investigate the knowledge, attitudes and practices (KAP) among college students toward physical literacy during COVID-19 school closure. Patients and Methods: This web-based cross-sectional study was conducted between December 9th, 2022 and December 24th, 2022 among college students during COVID-19 school closure. A self-designed questionnaire was developed to collect demographic information of the college students, and assess their KAP toward physical literacy. Results: A total of 969 students were recruited, with mean age of 18.73±0.97 years. The majority were male (54.70%), urban residents (78.02%), majoring in engineering (58.00%), and having exercise habits (61.09%). The mean KAP scores were 6.57±0.95, 32.63±4.07, and 27.06±7.23, respectively. Positive associations were identified between knowledge and attitude (OR = 2.01, 95% CI: 1.52-2.66, P < 0.001), and between attitude and practice (OR = 1.17, 95% CI: 1.12-1.22, P < 0.001). A bachelor's degree and being in the sophomore year were positively associated with knowledge (OR = 1.51-4.05, all P < 0.05). Urban residence and being in the sophomore year were negatively associated with attitude (OR = 0.43-0.59, all P < 0.05), while having daily exercise habits showed the opposite trend (OR = 1.85, 95% CI: 1.33-2.57, P < 0.001). Father's education level of high school and technical secondary school (OR = 0.58, 95% CI: 0.37-0.93, P = 0.023) and having daily exercise habits (OR = 3.88, 95% CI: 2.72-5.55, P < 0.001) were associated with practice. Conclusion: College students had sufficient knowledge, moderate attitudes and negative practices towards physical literacy during COVID-19 school closure. The findings hold significant potential for developing educational programs, fostering healthier lifestyles and promoting mental well-being among college students during public health outbreaks.

An ensemble penalized regression method for multi-ancestry polygenic risk prediction.

Great efforts are being made to develop advanced polygenic risk scores (PRS) to improve the prediction of complex traits and diseases. However, most existing PRS are primarily trained on European ancestry populations, limiting their transferability to non-European populations. In this article, we propose a novel method for generating multi-ancestry Polygenic Risk scOres based on enSemble of PEnalized Regression models (PROSPER). PROSPER integrates genome-wide association studies (GWAS) summary statistics from diverse populations to develop ancestry-specific PRS with improved predictive power for minority populations. The method uses a combination of L 1 (lasso) and L 2 (ridge) penalty functions, a parsimonious specification of the penalty parameters across populations, and an ensemble step to combine PRS generated across different penalty parameters. We evaluate the performance of PROSPER and other existing methods on large-scale simulated and real datasets, including those from 23andMe Inc., the Global Lipids Genetics Consortium, and All of Us. Results show that PROSPER can substantially improve multi-ancestry polygenic prediction compared to alternative methods across a wide variety of genetic architectures. In real data analyses, for example, PROSPER increased out-of-sample prediction R2 for continuous traits by an average of 70% compared to a state-of-the-art Bayesian method (PRS-CSx) in the African ancestry population. Further, PROSPER is computationally highly scalable for the analysis of large SNP contents and many diverse populations.

Polyoxometalate-Intercalated Tremella-Like CoNi-LDH Nanocomposites for Electrocatalytic Nitrite-Ammonia Conversion.

The electrocatalytic reduction of NO2- (NO2RR) holds promise as a sustainable pathway to both promoting the development of emerging NH3 economies and allowing the closing of the NOx loop. Highly efficient electrocatalysts that could facilitate this complex six-electron transfer process are urgently desired. Herein, tremella-like CoNi-LDH intercalated by cyclic polyoxometalate (POM) anion P8W48 (P8W48/CoNi-LDH) prepared by a simple two-step hydrothermal-exfoliation assembly method is proposed as an effective electrocatalyst for NO2- to NH3 conversion. The introduction of POM with excellent redox ability tremendously increased the electrocatalytic performance of CoNi-LDH in the NO2RR process, causing P8W48/CoNi-LDH to exhibit large NH3 yield of 0.369 mmol h-1 mgcat-1 and exceptionally high Faradic efficiency of 97.0% at -1.3 V vs the Ag/AgCl reference electrode in 0.1 M phosphate buffer saline (PBS, pH = 7) containing 0.1 M NO2-. Furthermore, P8W48/CoNi-LDH demonstrated excellent durability during cyclic electrolysis. This work provides a new reference for the application of POM-based nanocomposites in the electrochemical reduction of NO2- to obtain value-added NH3.

Human brain glycoform coregulation network and glycan modification alterations in Alzheimer's disease.

Despite the importance of protein glycosylation to brain health, current knowledge of glycosylated proteoforms or glycoforms in human brain and their alterations in Alzheimer's disease (AD) is limited. Here, we report a proteome-wide glycoform profiling study of human AD and control brains using intact glycopeptide-based quantitative glycoproteomics coupled with systems biology. Our study identified more than 10,000 human brain N-glycoforms from nearly 1200 glycoproteins and uncovered disease signatures of altered glycoforms and glycan modifications, including reduced sialylation and N-glycan branching and elongation as well as elevated mannosylation and N-glycan truncation in AD. Network analyses revealed a higher-order organization of brain glycoproteome into networks of coregulated glycoforms and glycans and discovered glycoform and glycan modules associated with AD clinical phenotype, amyloid-ß accumulation, and tau pathology. Our findings provide valuable insights into disease pathogenesis and a rich resource of glycoform and glycan changes in AD and pave the way forward for developing glycosylation-based therapies and biomarkers for AD.

Ratiometric electrochemiluminescence sensing and intracellular imaging of ClO- via resonance energy transfer.

Electrochemiluminescence resonance energy transfer (ECL-RET) is a versatile signal transduction strategy widely used in the fabrication of chem/biosensors. However, this technique has not yet been applied in visualized imaging analysis of intracellular species due to the insulating nature of the cell membrane. Here, we construct a ratiometric ECL-RET analytical method for hypochlorite ions (ClO-) by ECL luminophore, with a luminol derivative (L-012) as the donor and a fluorescence probe (fluorescein hydrazide) as the acceptor. L-012 can emit a strong blue ECL signal and fluorescein hydrazide has negligible absorbance and fluorescence signal in the absence of ClO-. Thus, the ECL-RET process is turned off at this time. In the presence of ClO-, however, the closed-loop hydrazide structure in fluorescein hydrazide is opened via specific recognition with ClO-, accompanied with intensified absorbance and fluorescence signal. Thanks to the spectral overlap between the ECL spectrum of L-012 and the absorption spectrum of fluorescein, the ECL-RET effect is gradually recovered with the addition of ClO-. Furthermore, the ECL-RET system has been successfully applied to image intracellular ClO-. Although the insulating nature of the cell itself can generate a shadow ECL pattern in the cellular region, extracellular ECL emission penetrates the cell membrane and excites intracellular fluorescein generated by the reactions between fluorescein hydrazide and ClO-. The cell imaging strategy via ECL-RET circumvents the blocking of the cell membrane and enables assays of intracellular species. The importance of the ECL-RET platform lies in calibrating the fluctuation from the external environment and improving the selectivity by using fluorescent probes. Therefore, this ratiometric ECL sensor has shown broad application prospects in the identification of targets in clinical diagnosis and environmental monitoring.

Monte Carlo-Based Optical Simulation of Optical Distribution in Deep Brain Tissues Using Sixteen Optical Sources.

Optical-based imaging has improved from early single-location research to further sophisticated imaging in 2D topography and 3D tomography. These techniques have the benefit of high specificity and non-radiative safety for brain detection and therapy. However, their performance is limited by complex tissue structures. To overcome the difficulty in successful brain imaging applications, we conducted a simulation using 16 optical source types within a brain model that is based on the Monte Carlo method. In addition, we propose an evaluation method of the optical propagating depth and resolution, specifically one based on the optical distribution for brain applications. Based on the results, the best optical source types were determined in each layer. The maximum propagating depth and corresponding source were extracted. The optical source propagating field width was acquired in different depths. The maximum and minimum widths, as well as the corresponding source, were determined. This paper provides a reference for evaluating the optical propagating depth and resolution from an optical simulation aspect, and it has the potential to optimize the performance of optical-based techniques.

Astaxanthin reduces inflammation and promotes a chondrogenic phenotype by upregulating SIRT1 in osteoarthritis.

OBJECTIVE: To investigate the effects of astaxanthin (AST) on mouse osteoarthritis (OA) and lipopolysaccharide (LPS)-induced ATDC5 cell damage and to explore whether SIRT1 protein plays a role. METHODS: In this study, some mouse OA models were constructed by anterior cruciate ligament transection (ACLT). Imaging, molecular biology and histopathology methods were used to study the effect of AST administration on traumatic OA in mice. In addition, LPS was used to stimulate ATDC5 cells to mimic the inflammatory response of OA. The effects of AST on the cell activity, inflammatory cytokines, matrix metalloproteinases and collagen type II levels were studied by CCK8 activity assay, reverse transcription polymerase chain reaction and protein imprinting. The role of SIRT1 protein was also detected. RESULTS: In the mouse OA model, the articular surface collapsed, the articular cartilage thickness and cartilage matrix protein abundance were significantly decreased, while the expression of inflammatory cytokines and matrix metalloproteinases was increased; but AST treatment reversed these effects. Meanwhile, AST pretreatment could partially reverse LPS-induced ATDC5 cell damage and upregulate SIRT1 expression, but this protective effect of AST was attenuated by concurrent administration of the SIRT1 inhibitor Ex527. CONCLUSION: AST can protect against the early stages of OA by affecting SIRT1 signalling, suggesting that AST might be a potential therapeutic agent for OA treatment.

A generalizable sensing platform based on molecularly imprinted polymer-aptamer double recognition and nanoenzyme assisted photoelectrochemical-colorimetric dual-mode detection.

Developing highly sensitive and selective methods that incorporate specific recognition elements is crucial for detecting small molecules because of the limited availability of small molecule antibodies and the challenges in obtaining sensitive signals. In this study, a generalizable photoelectrochemical-colorimetric dual-mode sensing platform was constructed based on the synergistic effects of a molecularly imprinted polymer (MIP)-aptamer sandwich structure and nanoenzymes. The MIP functionalized peroxidase-like Fe3O4 (Fe3O4@MIPs) and alkaline phosphatase mimic Zr-MOF labeled aptamer (Zr-mof@Apt) were used as the recognition elements. By selectively accumulating dibutyl phthalate (DBP), a small molecule target model, on Fe3O4@MIPs, the formation of Zr-MOF@Apt-DBP- Fe3O4@MIPs sandwich structure was triggered. Fe3O4@MIPs oxidized TMB to form blue-colored oxTMB. However, upon selective accumulation of DBP, the catalytic activity of Fe3O4@MIPs was inhibited, resulting in a lighter color that was detectable by the colorimetric method. Additionally, Zr-mof@Apt effectively catalyzed the hydrolysis of L-Ascorbic acid 2-phosphate sesquimagnesium salt hydrate (AAPS), generating ascorbic acid (AA) that could neutralize the photogenerated holes to decrease the photocurrent signals for PEC sensing and reduce oxTMB for colorimetric testing. The dual-mode platform showed strong linearity for different concentrations of DBP from 1.0 pM to 10 µM (PEC) and 0.1 nM to 0.5 µM (colorimetry). The detection limits were 0.263 nM (PEC) and 30.1 nM (colorimetry) (S/N = 3), respectively. The integration of dual-signal measurement mode and sandwich recognition strategy provided a sensitive and accurate platform for the detection of small molecules.

Genome-Wide Association Analysis of Effective Tillers in Rice under Different Nitrogen Gradients.

Nitrogen is a crucial element that impacts rice yields, and effective tillering is a significant agronomic characteristic that can influence rice yields. The way that reduced nitrogen affects effective tillering is a complex quantitative trait that is controlled by multiple genes, and its genetic basis requires further exploration. In this study, 469 germplasm varieties were used for a genome-wide association analysis aiming to detect quantitative trait loci (QTL) associated with effective tillering at low (60 kg/hm2) and high (180 kg/hm2) nitrogen levels. QTLs detected over multiple years or under different treatments were scrutinized in this study, and candidate genes were identified through haplotype analysis and spatio-temporal expression patterns. A total of seven genes (NAL1, OsCKX9, Os01g0690800, Os02g0550300, Os02g0550700, Os04g0615700, and Os04g06163000) were pinpointed in these QTL regions, and were considered the most likely candidate genes. These results provide favorable information for the use of auxiliary marker selection in controlling effective tillering in rice for improved yields.

Promoting the disassemble and enzymatic saccharification of bamboo shoot shells via efficient hydrated alkaline deep eutectic solvent pretreatment.

Pretreatment is a key process restricting the development of biorefinery. This work developed a pretreatment process based on an ethanolamine/acetamide alkaline deep eutectic solvent (ADES). Under microwave assistance, pure ADES pretreatment at 100 °C for 10 min achieved 95.9 % delignification and 95.2 % hemicellulose removal of bamboo shoot shells (BSS). Further, when 75 % water was added to pure DES to prepare hydrated DES (75 %-HADES), impressive delignification (93.2 %), hemicellulose removal (92.2 %) and cellulose recovery (94.8 %) were still achieved. The cellulose digestibility of the 75 %-HADES pretreated solid residue was significantly increased from 12.2 % (the control) to 91.2 %. Meanwhile, the structural features of hemicellulose and lignin macromolecules fractionated by 75 %-HADES pretreatment were well preserved, offering opportunities for downstream utilization. Overall, this work proposes an effective pretreatment strategy with the potential to enable the utilization of all major components of bamboo shoot shells.

High-Humidity-Tolerant Chloride Solid-State Electrolyte for All-Solid-State Lithium Batteries.

Halide solid-state electrolytes (SSEs) hold promise for the commercialization of all-solid-state lithium batteries (ASSLBs); however, the currently cost-effective zirconium-based chloride SSEs suffer from hygroscopic irreversibility, low ionic conductivity, and inadequate thermal stability. Herein, a novel indium-doped zirconium-based chloride is fabricated to satisfy the abovementioned requirements, achieving outstanding-performance ASSLBs at room temperature. Compared to the conventional Li2ZrCl6 and Li3InCl6 SSEs, the hc-Li2+xZr1-xInxCl6 (0.3 ≤ x ≤ 1) possesses higher ionic conductivity (up to 1.4 mS cm-1), and thermal stability (350 °C). At the same time, the hc-Li2.8Zr0.2In0.8Cl6 also shows obvious hygroscopic reversibility, where its recovery rate of the ionic conductivity is up to 82.5% after 24-h exposure in the 5% relative humidity followed by heat treatment. Theoretical calculation and experimental results reveal that those advantages are derived from the lattice expansion and the formation of Li3InCl6 ·2H2O hydrates, which can effectively reduce the migration energy barrier of Li ions and offer reversible hydration/dehydration pathway. Finally, an ASSLB, assembled with reheated-Li2.8Zr0.2In0.8Cl6 after humidity exposure, single-crystal LiNi0.8Mn0.1Co0.1O2 and Li-In alloy, exhibits capacity retention of 71% after 500 cycles under 1 C at 25 °C. This novel high-humidity-tolerant chloride electrolyte is expected to greatly carry forward the ASSLBs industrialization.

Flexible Multimodal Sensing System Based on a Vertical Stacking Strategy for Efficiently Decoupling Multiple Signals.

Multisensory integration enables the simultaneous perception of multiple environmental stimuli while minimizing size and energy consumption. However, conventional multifunctional integration in flexible electronics typically requires large-scale horizontal sensing arrays (such as flexible printed circuit boards), posing decoupling complexities, tensile strain limitation, and spatial constraints. Herein, a fully flexible multimodal sensing system (FMSS) is developed by coupling biomimetic stretchable conductive films (BSCFs) and strain-insensitive communication interfaces using a vertical stacking integration strategy. The FMSS achieves vertical integration without additional adhesives, and it can incorporate individual sensing layers and stretchable interconnects without any essential constraint on their deformations. Accordingly, the temperature and pressure are precisely decoupled simultaneously, and tensile stress can be accurately discerned in different directions. This vertical stacking integration strategy is expected to offer a new approach to significantly streamline the design and fabrication of multimodal sensing systems and enhance their decoupling capabilities.

Photoacoustic/ultrasound dual-modality imaging for marker clip localization in neoadjuvant chemotherapy of breast cancer.

Significance: To ensure precise tumor localization and subsequent pathological examination, a metal marker clip (MC) is placed within the tumor or lymph node prior to neoadjuvant chemotherapy for breast cancer. However, as tumors decrease in size following treatment, detecting the MC using ultrasound imaging becomes challenging in some patients. Consequently, a mammogram is often required to pinpoint the MC, resulting in additional radiation exposure, time expenditure, and increased costs. Dual-modality imaging, combining photoacoustic (PA) and ultrasound (US), offers a promising solution to this issue. Aim: Our objective is to localize the MC without radiation exposure using PA/US dual-modality imaging. Approach: A PA/US dual-modality imaging system was developed. Utilizing this system, both phantom and clinical experiments were conducted to demonstrate that PA/US dual-modality imaging can effectively localize the MC. Results: The PA/US dual-modality imaging can identify and localize the MC. In clinical trials encompassing four patients and five MCs, the recognition rate was ∼80%. Three experiments to verify the accuracy of marker position recognition were successful. Conclusions: We effectively localized the MC in real time using PA/US dual-modality imaging. Unlike other techniques, the new method enables surgeons to pinpoint nodules both preoperatively and intraoperatively. In addition, it boasts non-radioactivity and is comparatively cost-effective.

Association of tumor budding with clinicopathological features and prognostic value in stage III-IV colorectal cancer.

BACKGROUND: Tumor budding (TB) has emerged as a promising independent prognostic biomarker in colorectal cancer (CRC). The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC. However, existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies. Consequently, this study investigated the correlation among TB categories, clinicopathological features, and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification. AIM: To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC. METHODS: The clinical data of 547 CRC patients were collected for this retrospective study. Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines. RESULTS: Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy (P = 0.004), clinical stage IV (P < 0.001), ≥ 4 regional lymph node metastases (P = 0.004), left-sided colonic cancer (P = 0.040), and Bd 2-3 (P = 0.002) were independent prognostic factors in patients with stage III-IV CRC. Moreover, the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3, both in the tumor stroma and its invasive margin. CONCLUSION: TB has an independent predictive prognostic value in patients with stage III-IV CRC. It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.

Characterization of A π-π stacking cocrystal of 4-nitrophthalonitrile directed toward application in photocatalysis.

Photoexcitation of the electron-donor-acceptor complexes have been an effective approach to achieve radicals by triggering electron transfer. However, the catalytic version of electron-donor-acceptor complex photoactivation is quite underdeveloped comparing to the well-established utilization of electronically biased partners. In this work, we utilize 4-nitrophthalonitrile as an electron acceptor to facilitate the efficient π-stacking with electron-rich aromatics to form electron-donor-acceptor complex. The characterization and energy profiles on the cocrystal of 4-nitrophthalonitrile and 1,3,5-trimethoxybenzene disclose that the electron transfer is highly favorable under the light irradiation. This electron acceptor catalyst can be efficiently applied in the benzylic C-H bond photoactivation by developing the Giese reaction of alkylanisoles and the oxidation of the benzyl alcohols. A broad scope of electron-rich aromatics can be tolerated and a mechanism is also proposed. Moreover, the corresponding π-anion interaction of 4-nitrophthalonitrile with potassium formate can further facilitate the hydrocarboxylation of alkenes efficiently.